Method for separation of 90Y from 90Sr

ABSTRACT

Inorganic ion exchange materials for the separation of  90 Y from  90 Sr include chabazite, clinoptilolite, potassium pharmacosiderite, sodium titanosilicate and sodium nonatitanate. These materials are suitable for making a  90 Y generator that contains  90 Sr immobilized on an ion exchange column of the materials. The materials have a very high selectivity for  90 Sr, a very low selectivity for  90 Y, good radiation and thermal stability, low toxicity, fast reaction kinetics, and can be readily and reproducibly synthesized. A method is thus provided for eluting  90 Y from the ion exchange material with an eluant solution. The eluant solution is preferably aqueous, preferably has a pH greater than about 5, and preferably includes a chelating agent. Preferred chelating agents include gluconic acid, oxalic acid, iminodiacetic acid, nitrilotriacetic acid, citric acid, and combinations thereof.

[0001] This application is a continuation-in-part of U.S. applicationSer. No. 10/173,971 filed on Jun. 18, 2002.

BACKGROUND OF THE INVENTION

[0002] 1. Field of the Invention

[0003] This invention relates to methods, apparatus and compositions forseparating yttrium-90 from strontium-90.

[0004] 2. Background of the Related Art

[0005] The use of radioactive isotopes as diagnostic, imaging andtherapeutic agents is a relatively new area of medicine that hasflourished in the last fifty years. A number of radioisotopes, primarilybeta emitting radionuclides, are finding use in the in vitro treatmentof cancers to destroy or sterilize cancer cells. The treatment isadministered in a series of cycles to avoid radiotoxicity to other areasof the body, particularly the kidneys and bone marrow. The isotopes ofinterest are commonly attached to monoclonal antibodies or polypeptidesspecific for the cancer cells to be treated, thus delivering a dose ofradiation directly to a tumor. This technique is termedradioimmunotherapy (RIT) and is increasingly being used to complementexisting surgical techniques and chemotherapy.

[0006] In order to fuel the current research in the use of radionuclidesto treat cancers, it is essential that new isotope production methods bedeveloped to increase the availability and decrease the cost ofradioisotopes. For medicinal applications, the radioisotope suppliedneeds to be radiochemically pure to prevent the accidental introductionof unwanted additional radionuclides into a patient, and, preferably, becarrier free. A fundamental aspect of increasing the availability ofradioisotopes to medical personnel is the development of new,inexpensive, radiolytically stable materials to allow the necessaryseparations to be achieved.

[0007]⁹⁰Y is a high-energy beta emitter that is finding use in thetreatment of certain forms of cancer. ⁹⁰Y decays by pure beta emission,with a half-life (T_(½)) of 64 hours, to stable ⁹⁰Zr. The energetic betaparticles (2.3 MeV) can penetrate an average of 0.5 cm in human tissue,with a maximum penetration of up to 1 cm. Consequently, they are usefulin the treatment of cancerous tumors like those found in Hodgkin'sdisease, where tumors are typically between 1 and 5 cm in diameter. The⁹⁰Y can be successfully attached to an antibody or peptide fragment,which will then transport the ⁹⁰Y to the targeted tumor.

[0008] In order to use 90Y in the treatment of cancers, it is necessaryto obtain a very pure source of the isotope that is free from the parent⁹⁰Sr. This is essential because ⁹⁰Sr has a 28 year half-life and islikely to accumulate in the bone if inadvertently introduced into thebody. The maximum tolerable amount of ⁹⁰Sr fixed in the bone is only 2μCi and consequently great care needs to be performed to achieve thenecessary Sr/Y separation to ensure minimal introduction of ⁹⁰Sr intothe body during the ⁹⁰Y radiotherapy.

[0009]⁹⁰Y is the daughter product of ⁹⁰Sr, an abundant fission productof ²³⁵U, found in nuclear wastes resulting from the reprocessing ofspent commercial nuclear fuel and in the separation of ²³⁹Pu for weaponsmanufacture. ⁹⁰Sr has a half-life of approximately 28 years. Theradioactive decay scheme is outlined in Equation 1 below.

⁹⁰Sr(β⁻)→⁹⁰Y(β⁻)→⁹⁰Zr  (1)

[0010] In order to obtain a supply of ⁹⁰Y, it is first necessary toseparate ⁹⁰Sr from other isotopes in the nuclear waste. This can readilybe achieved using selective precipitation, ion exchange or solventextraction techniques to produce a crude ⁹⁰Sr ‘cow’ for use as a sourceof ⁹⁰Y. ⁹⁰Y can also be produced by the neutron irradiation of ⁸⁹Yoxide, Y₂O₃, for a period ranging from several days to a week, but thisis expensive and the ⁹⁰Y product contains large amounts of inactive ⁸⁹Ymaking it unsuitable for medicinal applications.

[0011] There are a number of methods described in the literature for theseparation of the ⁹⁰Y daughter from the parent ⁹⁰Sr, including solventextraction, ion exchange, precipitation and chromatographic procedures.Of these methods, ion exchange techniques have probably received themost attention. However, all of the current methods suffer fromdrawbacks. For instance, in some separation procedures, the ⁹⁰Sr is heldonto an organic cation exchange resin and the ⁹⁰Y is eluted using anaqueous complexant solution, such as EDTA, oxalate, lactate, citrateetc. Consequently, the purified ⁹⁰Y is generated as a complex that isnot suitable for the direct labeling of antibodies and requires furtherprocessing. Organic ion exchange resins are also prone to radiationdamage resulting in a decrease in capacity and the potential release oftoxic organic molecules into the ⁹⁰Y stream as the resin decomposes.Consequently, there is a need for new material and methods to producepure ⁹⁰Y.

[0012] The method disclosed by Bray and Webster in U.S. Pat. No.5,512,256 uses a solvent extraction process to separate ⁹⁰Y from ⁹⁰Sr. A0.3M solution of di(2-ethylhexyl)phosphoric acid (HDEHP) in n-dodecaneis used to extract ⁹⁰Y from a solution of ⁹⁰Sr/⁹⁰Y in 0.3M nitric acid.The HDEHP selectively extracts the ⁹⁰Y into the organic phase andresidual ⁹⁰Sr can be removed by further washing the organic fractionwith fresh 0.3M nitric acid. Although this method is very effective atseparating ⁹⁰Y from ⁹⁰Sr, multiple steps are required and the recoveryof both the ⁹⁰Sr cow and ⁹⁰Y fractions requires multiple washing andstripping phases. This produces waste organic and aqueous streams thatneed to be treated and disposed of safely. There will also be someradiolysis of both the organic complexant and the solvents that willlimit their useful life and also may cause the release of unwantedorganic species into solution. This is the primary method utilized toproduce ⁹⁰Y in the USA today.

[0013] In U.S. Pat. No. 5,368,736, Horwitz and Dietz use a multiple stepchromatographic process to separate ⁹⁰Sr from ⁹⁰Y. The ⁹⁰Sr stocksolution in 3M nitric acid is passed through three strontium selectivechromatographic ion exchange columns in series so that the solutionexiting the third column contains essentially only ⁹⁰Y, the ⁹⁰Sr beingretained on the columns. This raw ⁹⁰Y solution is the passed through arare earth selective column that selectively extracts the ⁹⁰Y. Thepurified ⁹⁰Y can then be eluted off the column. However, thechromatographic columns contain organic resins that are susceptible toradiation damage and may leach undesirable radiolysis fragments into thepurified ⁹⁰Y stream. Radiation damage is kept to a minimum by loadingand then eluting the radioactivity from the columns, but this methodalso requires the use of a dedicated hot cell facility, necessitatingshipment of the purified ⁹⁰Y to the end user.

[0014] Huntley's U.S. Pat. No. 5,494,647 discloses an ion exchangeprocess for separating ⁹⁰Y from ⁹⁰Sr using CHELEX-100® (Bio-RadLaboratories, Richmond, Calif.), a chelating ion exchange resin.CHELEX-100® is an organic ion exchange resin that consists ofiminodiacetic acid groups mounted on a polystyrene/divinyl benzenesubstrate. The method is designed for use with environmental samplesonly containing trace amounts of ⁹⁰Sr, and it is disclosed that themethod does not work effectively at high strontium concentrations. Theorganic resin would also be susceptible to radiation damage and it isdoubtful that the method would be able to produce the level of ⁹⁰Ypurity required for medicinal applications.

[0015] Therefore, there is a need for improved methods, apparatus, andcompositions for separating yttrium-90 from strontium-90. It would bedesirable if the compositions were highly radiation resistant, thermallystable, chemically stable, and non-toxic. It would be even moredesirable if the compositions and methods provided very high affinitiesfor strontium-90 and very low affinities for yttrium-90.

SUMMARY OF THE INVENTION

[0016] The present invention provides a process for separatingstrontium-90, comprising the adsorption of strontium-90 onto aninorganic ion exchange material from a solution containing a source ofstrontium-90. The solution is preferably neutral or near neutral. Theprocess may entail selecting the inorganic ion exchange material fromchabazite, clinoptilolite, pharmacosiderite, titanosilicate,nonatitanate, and combinations thereof.

[0017] In one embodiment, the inorganic ion exchange material is sodiumnonatitanate prepared by reacting titanium isopropoxide and aqueoussodium hydroxide at a temperature between 100° C. and 250° C. for aperiod between 12 hours and 2 weeks. Optionally, the inorganic ionexchange material is sodium titanosilicate prepared by hydrothermallyheating a titanium silicate gel in NaOH. Said titanium silicate gel maybe hydrothermally heated in 6M NaOH at 170° C. for 2 days.

[0018] In another embodiment, the inorganic ion exchange material is atitanosilicate having the general formula:

M₃H(AO)₄(BO₄)₃ .xH₂O

[0019] where: M is a cation selected from H, K, Na, Rb, Cs and mixturesthereof;

[0020] A is selected from Ti and Ge; and

[0021] B is selected from Si and Ge; and

[0022] x is a value between 4 and 6.

[0023] A further embodiment of the invention provides a yttrium-90generator prepared according to the aforementioned process. Thisgenerator may comprise inorganic ion exchange material selected fromclinoptilolite, chabazite, pharmacosiderite, titanosilicate, sodiumnonatitanate, or other inorganic compounds with a high affinity forstrontium, and combinations thereof. The inorganic ion exchange materialmay be formed into pellets having a diameter between 0.2 and 0.5 mm.Optionally, the pellets comprise polyacrylonitrile, or another polymer,as a binder. Alternatively, the pellets may comprise amorphous titaniumdioxide, clay, amorphous silica, amorphous zirconia, or anotherinorganic oxide as the binder.

[0024] An additional embodiment provides a process for separatingyttrium-90 from strontium-90, comprising preparing a solution ofstrontium-90 then adsorbing strontium-90 from the solution onto aninorganic ion exchange material, and eluting yttrium-90 from theinorganic ion exchange material with an aqueous solution. The processmay further comprise the step of allowing yttrium-90 to grow into theinorganic ion exchange material. These steps may be repeated.Optionally, the inorganic ion exchange material is selected fromclinoptilolite, chabazite, pharmacosiderite, titanosilicate,nonatitanate, or other inorganic compounds with a high affinity forstrontium, and combinations thereof. Preferably, the yttrium-90 iseluted with a solution including a chelating agent.

BRIEF DESCRIPTION OF THE DRAWINGS

[0025] So that the above recited features and advantages of the presentinvention can be understood in detail, a more particular description ofthe invention, briefly summarized above, may be had by reference to theembodiments thereof that are illustrated in the appended drawings. It isto be noted, however, that the appended drawings illustrate only typicalembodiments of this invention and are therefore not to be consideredlimiting of its scope, for the invention may admit to other equallyeffective embodiments.

[0026]FIG. 1 is a diagram illustrating the structure of clinoptiloliteillustrating the regular channels within the structure that give rise toion sieving properties.

[0027]FIG. 2 is a diagram illustrating the layered structure of sodiumnonatitanate, Na4Ti₉O₂₀.xH₂O. Sodium ions (solid circles) and watermolecules are located between layers of TiO₆ octahedra.

[0028]FIG. 3 is a diagram illustrating the structure of the Cs-exchangedform of the titanosilicate, NaTS.

[0029]FIG. 4 is a diagram illustrating the structure of the potassiumform of the pharmacosiderite titanosilicate, KTS-Ph.

[0030]FIG. 5 is a schematic representation of the structure of syntheticchabazite, showing the exchangeable cation sites located on the insidesof the large tubes

[0031]FIG. 6 is a graph of x-ray diffraction patterns showing the effectof hydrothermal treatment on the crystallinity of sodium nonatitanate,including: (A) TA-A-18, no treatment, (B) TA-A-19, 21 hr. at 170° C.,and (C) TA-A-17, 7 days at 170° C.

[0032]FIG. 7 shows the formula and structures of five suitablecomplexants.

[0033]FIG. 8 is a three-dimensional bar chart of the ratio ofdistribution coefficients for strontium and yttrium for nine ionexchange materials and five complexants tested.

[0034]FIG. 9 is a schematic diagram of a column filled with an ionexchange material, such as sodium titanosilicate.

[0035]FIG. 10 is a three dimensional bar chart of the yttrium yield fromchabazite (AW-500) with a series of eluants. The two rows of columnsrepresent the results for the two columns being tested.

[0036]FIG. 11 is a three dimensional bar chart of the yttrium yield fromsodium titanosilicate (TA-A-13) with a series of eluants.

[0037]FIG. 12 is a three dimensional bar chart of the yttrium yield fromclinoptilolite with a series of eluants.

[0038]FIG. 13 is a three dimensional bar chart of the strontium lostfrom clinoptilolite with a series of eluants.

[0039]FIG. 14 is a three dimensional bar chart of the yttrium yield frompotassium pharmacosiderite (TA-A-2) with a series of eluants.

[0040]FIG. 15 is a three dimensional bar chart of the strontium lostfrom potassium pharmacosiderite (TA-A-2) with a series of eluants.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0041] This present invention provides inorganic ion exchange materialsto separate ⁹⁰Y from ⁹⁰Sr in neutral to alkaline media. These inorganicion exchange materials include chabazite (such as sodium chabazite),clinoptilolite (such as sodium clinoptilolite), pharmacosiderite (suchas potassium pharmacosiderite (KTS-Ph)), titanosilicate (such as sodiumtitanosilicate (NaTS)), and nonatitanate (such as sodium nonatitanate(NaTi)). All of the ion exchangers are purely inorganic, highlyradiation resistant, thermally stable, chemically stable, and non-toxic.Because of this stability, no release of toxic organic fragments isexperienced, no reduction in ion exchange capacity occurs, and largelevels of activity may be loaded onto a generator. Stability of thegenerator is essential because it has been estimated that the radiationdose in a ⁹⁰Y generator containing 30 Ci of ⁹⁰Sr/⁹⁰Y is as high as 10⁹rad/day. A comparison of the characteristics of organic ion exchangeresins and inorganic ion exchangers is given in Table 1. TABLE 1Comparison of organic ion exchange resins and inorganic ion exchangematerials Property Organic Resins Inorganic Ion Exchangers ThermalStability Low High Ion Selectivity Low to Moderate Moderate to HighRadiation Stability Low High Physical Form Beads, Granules, etc. Usuallypowders Cost Moderate Variable

[0042] Clinoptilolite is a naturally occurring zeolite and has the idealformula Na₆Al₆Si₃₀O₇₂24 H₂O. It is a member of the Heulandite group ofzeolites and has a layered porous structure, which is depicted inFIG. 1. The ion selectivity arises due to the regular pores and channelswithin the zeolite structure which give rise to an ion sieving effect.The sodium ions are readily exchangeable for other cations and, innature, K⁺, Mg²⁺ and Ca²⁺ are generally also found on the exchange sitesalong with minor quantities of a range of other cations. Clinoptilolitehas a particularly high selectivity towards Cs⁺ and Sr²⁺ ions. Thecation exchange capacity of clinoptilolite is, however, fairly low andis only approximately 2.2 meq/g for the fully sodium-exchanged form.

[0043] Sodium nonatitanate, Na₄Ti₉O₂₀xH₂O, is synthesized byhydrothermally treating a titanium salt, such as titanium isopropoxide,in strong base at a temperature of between 150° C. and 250° C. Thereaction is outlined in Equation 2.

9 Ti(OC₃H₇)₄+4 NaOH_((aq))→Na₄Ti₉O₂₀ .xH₂O+9 C₃H₇OH  (2)

[0044] The resulting sodium nonatitanate material is only poorlycrystalline and its precise structure has not been determined. However,experiments have suggested that it consists of layers of TiO₆ octahedraseparated by water molecules and sodium cations, as shown in FIG. 2. Thesodium cations are weakly held and readily exchanged for strontium andother cations. The layers of TiO₆ octahedra are generally separated by aspace of 10 Å, though this distance can vary according to the amount ofwater intercalated between the layers. The nonatitanate has a highselectivity for strontium at pH greater than 7, but a negligibleselectivity in more acidic conditions. Thus, strontium absorbed onto thematerial can be readily stripped with dilute mineral acid allowing theion exchanger to be reused. The titanate also has good thermal,radiolytic and chemical stability and is expected to have a lowtoxicity. The theoretical cation exchange capacity (CEC) is 4.74 meq/g,which compares favorably with organic ion exchange resins.

[0045] Sodium titanosilicate (NaTS) has the ideal formulaNa₂Ti₂O₃SiO₄.2H₂O. This material can be synthesized in a crystallineform that has allowed its structure to be determined using X-Ray powdermethods. The titanosilicate was found to have a tetragonal unit cellwith a=b=7.8082(2) Å and c=11.9735(4) Å. Edge-sharing TiO₆ clustersreside in all eight corners of the unit cell and silicate tetrahedra arelocated midway between the clusters and link them together. Thisarrangement produces tunnels parallel to the c axis where theexchangeable sodium ions and the water molecules reside. The remainingsodium ions are located in the framework, bonded by silicate oxygens andare thus not exchangeable. The structure of this ion exchange materialis illustrated in FIG. 3.

[0046] Due to steric repulsions and space limitations, some of thesodium ions in the tunnels of the sodium titanosilicate are replaced byprotons leading to an actual formula ofNa_(1.64)H_(0.36)Ti₂O₃SiO₄.1.84H₂O. This exchanger was synthesized byhydrothermally heating a titanium silicate gel of appropriatestoichiometry of four moles of titanium for each mole of silicon in 6MNaOH at 170° C. for 2 days. This material has been shown to have a highselectivity for Cs⁺ ions in both acid and alkaline pH and a highselectivity for strontium in alkaline media. Strontium is readilyremoved by washing with dilute acid.

[0047] The second class of titanosilicate materials has the crystalstructure of the natural mineral pharmacosiderite. Pharmacosiderite hasthe ideal formula KFe₄(AsO₄)₃(OH)₄ and crystallizes in the cubic system.Titanosilicates with the general formula M₃H(AO)₄(BO₄)₃.4-6H₂O (M=H, K,Na, etc.; A=Ti, Ge; B=Si, Ge) were prepared using hydrothermaltechniques. A homogenous gel of appropriate stoichiometry of four molesof titanium for each three moles of silicon was hydrothermally treatedin an excess of either KOH or CsOH at 200° C. for 1 to 3 days. Sodiumand proton forms were then prepared by exhaustively ion exchanging thematerial with either NaCl or HCl. The most studied material of these isthe potassium pharmacosiderite, K₃H(TiO)₄(SiO₄)₃.4H₂O (KTS) in whicha=b=c=7.7644(3)Å. Each unit cell consists of clusters of four titaniaoctahedra linked to each other by silicate groups as shown in FIG. 4.This produces a series of intersecting tunnels parallel to the a, b andc axes with the exchangeable ions residing close to the face-centers ofthe unit cell. Pharmacosiderites have shown very high affinities towardsstrontium ions in alkaline solutions.

[0048] Chabazite is a well-characterized synthetic zeolite havingexchangeable cation sites located on the insides of the large tubes.FIG. 5 is a schematic representation of the structure of syntheticchabazite.

⁹⁰Y/⁹⁰Sr Separation Process

[0049] One embodiment of the present invention provides a separationmethod that comprises the following steps:

[0050] (1) A source of ⁹⁰Sr is loaded onto the inorganic ion exchangematerial from a solution of dilute sodium salt, the loaded exchanger isslurried into a column, and the column is washed with fresh sodiumnitrate solution to remove any residual radioactivity not bound to theexchanger.

[0051] (2) ⁹⁰Y is allowed to grow into the column.

[0052] (3) ⁹⁰Y is eluted using a dilute solution of a sodium salt orsimilar eluant at a pH of 7 or greater. ⁹⁰Sr is strongly held by the ionexchanger and remains on the column.

[0053] (4) Optionally, the eluted ⁹⁰Y is then passed through a small,secondary microcolumn of the ion exchange material to remove anyresidual traces of ⁹⁰Sr that may have been eluted from the primary ionexchange column. This small column, anticipated to be similar in size toa syringe filter, may be considered to be regarded as disposable and afresh column is used for each ⁹⁰Y elution.

[0054] Thus, ⁹⁰Y is obtained as Y³⁺ ions (carrier-free) in a sodium saltsolution and the ⁹⁰Y is in a suitable form for attaching to monoclonalantibodies or for other processing. The separation process is rapid andsimple requiring a minimum of steps or chemical additives. The proposedmethod is also amenable to the production of a ⁹⁰Y generator that can be‘milked’ at the point of use to produce ⁹⁰Y on demand. Only the initialloading of the generator needs to be performed in a hot cell. Sinceneither the parent or daughter isotopes is a gamma emitter, shieldingshould not prove problematical allowing high ⁹⁰Sr activities to beloaded onto a generator. However, some lead shielding will likely benecessary due to the Bremsstrahlung radiation produced by largequantities of ⁹⁰Y.

[0055] The ⁹⁰Y product is also unlikely to contain any contaminants,such as Fe³⁺, that could compete with Y³⁺ during the synthesis of the⁹⁰Y-labelled antibody. Cationic impurities will either be strongly heldonto the ion exchange material and not eluted during the ⁹⁰Y milking, orwill be poorly absorbed onto the ion exchanger during the initial ⁹⁰Srloading and eluted when the column is washed prior to the first ⁹⁰Ymilking.

[0056] All three of these structures feature anionically chargedframeworks with open channels to accommodate exchangeable cations. Sixadditional ion exchange materials were synthesized: potassiumpharmacosiderite, sodium titanosilicate, (where structure is in FIG. 3),sodium nonatitanate (with three degrees of crystallinity), and sodiumclinoptilolite.

[0057] All of the compounds listed above have been shown to have astrong affinity for strontium, a key factor for use as an yttriumgenerator. It is also important that the yttrium daughter is notretained by the ion exchange material. Fortunately Sr²⁺ and Y³⁺ havesignificantly different properties, with the smaller, more highlycharged Y³⁺ surrounding itself with a larger shell of water molecules.This makes it easier for an ion exchange material with a threedimensional structure to discriminate between the two.

[0058] Yttrium is easily precipitated under conditions of low acidity(pH>3 or 4). Most ion exchange materials retain strontium poorly at lowpH, so the column must be operated under neutral or basic conditions.Keeping yttrium in solution under these conditions requires the use of acomplexant.

[0059] Five compounds known to chelate yttrium were tested to determinethe efficacy for keeping yttrium in solution under non-acidicconditions. These compounds, all of which contain at least twocarboxylic acid functionalities, are listed in Table 2. TABLE 2Compounds tested for solubilizing yttrium Gluconic Acid Oxalic AcidIminodiacetic Acid Nitrilotriacetic Acid (NTA) Citric Acid

[0060] All of the compounds in Table 2 were found to be effective forcomplexing yttrium to varying degrees. When tested for strontium theywere found to be far less effective, with the strontium remaininglargely uncomplexed. Adding a complexant was found to improve theseparation between the two elements, with the solubility of the yttriumimproved under both neutral and basic conditions leading to thestrontium remaining sequestered on the ion exchanger while the yttriumremains in solution.

[0061] While this type of basic data is useful for characterizing thematerials, it is not sufficient to demonstrate an effective isotopegenerator. This can be demonstrated best by loading a column with theion exchange material, loading the ion exchange material with ⁹⁰Sr, anddemonstrating the elution of pure ⁹⁰Y. In a series of column tests(described in the examples) the four inorganic ion exchange materialsdescribed here showing the greatest difference in their affinities foryttrium and strontium ions (sodium titanosilicate, chabazite,clinoptilolite, and potassium pharmacosiderite) were found to be usefulfor generating ⁹⁰Y solutions from a ⁹⁰Sr source. Some of these compounds(chabazite and sodium titanosilicate) were found to be sufficientlyeffective to serve as generators for ⁹⁰Y suitable for medical use.

[0062] There are two criteria required of an ion exchange material foruse in a ⁹⁰Y generator. Those criteria are that the material has a muchhigher affinity for strontium than it does for yttrium and that thematerial is stable when exposed to intense radiation. All of thematerials tested were selected so that they would meet the latterrequirement. This is the specific advantage of inorganic ion exchangematerials over organic ones.

[0063] All of the ion exchange materials tested also meet the first ofthese requirements to some degree. Two of the materials, chabazite andsodium titanosilicate, are extremely effective and deliver Sr-freeyttrium suitable for use in the preparation of radiopharmaceuticals.Both of those compounds reliably deliver the ⁹⁰Y produced by the decayof ⁹⁰Sr isolated within their structures when eluted with a solutioncontaining a complexant. Both elute a solution completely free of ⁹⁰Sr,a requirement for any medical application of ⁹⁰Y. The other ionexchangers tested are also useful. Although they are not presentlybelieved to be as effective, they still have utility.

EXAMPLE 1 Synthesis of Potassium Pharmacosiderite

[0064] The starting material for potassium pharmacosiderite was 20 g ofsilica gel (Aldrich Chemical Company, Milwaukee, Wis., Grade 923) whichwas initially combined with 80 mL of 10 M KOH. In a separate beaker, 62mL of titanium isopropoxide (97%, Aldrich), 40 mL of 30% H₂O₂, 200 mL ofdeionized water and 60 mL of 10M KOH were added together with vigorousstirring. The contents of the two beakers were then combined, stirred tohomogenize the mixture, placed in a 1 L Teflon-lined hydrothermalvessel, and heated at 190° C. for 4 days. The product was centrifuged,washed with absolute ethanol, dried overnight at 60° C. then ground to afine powder. The structure of the product was confirmed by x-ray powderdiffraction (XRD). This material was labeled TA-A-2.

EXAMPLE 2 Synthesis of Sodium Titanosilicate

[0065] To synthesize sodium titanosilicate 33.3 g oftetraethoxyorthosilicate (98%, Aldrich) was combined with 45.6 g oftitanium isopropoxide (97%, Aldrich) and added to 260 mL of 6.32 M NaOH.The resultant white gel was stirred well to ensure homogeneity, placedin a 1 L Teflon-lined hydrothermal vessel, and heated at 170° C. for 2days. The product was centrifuged, washed with absolute ethanol, driedovernight at 60° C. then ground to a fine powder. The structure of theproduct was confirmed by XRD. This material, the structure of which isshown in FIG. 3, was labeled TA-A-13.

EXAMPLE 3 Synthesis of Sodium Nonatitanate

[0066] Three versions of sodium nonatitanate were prepared. Each of thethree started with 77.5 g of titanium isopropoxide (97%, Aldrich) whichwas placed in a round-bottomed Teflon flask. While stirring constantly,84.35 g of a 50 wt % solution of NaOH was added resulting in a whitegelatinous precipitate. 60 mL of deionized water was added and themixture was stirred for one hour and then heated at approximately 108°C. for an additional 3 hours with a water cooled reflux condenser usedto prevent excessive loss of water. At this stage the raw sodiumnonatitanate is ready for further processing.

EXAMPLE 4 Highly Crystalline Sodium Nonatitanate

[0067] One batch of material produced as described in example 3 was thentransferred to a 1 L Teflon-lined hydrothermal vessel using 90 mL ofdeionized water and heated at 170° C. for 7 days. The product wascentrifuged, washed with absolute ethanol, dried overnight at 60° C.then ground to a fine powder and designated TA-A-17.

EXAMPLE 5 Poorly Crystalline Sodium Nonatitanate

[0068] A second batch of material produced as described in example 3,designated TA-A-18, received no hydrothermal treatment. It wascentrifuged, washed with absolute ethanol, dried overnight at 60° C. andthen ground to a fine powder.

EXAMPLE 6 Partially Crystalline Sodium Nonatitanate

[0069] A third batch of material produced as described in example 3,designated TA-A-19, was transferred to a 1 L Teflon-lined hydrothermalvessel using 90 mL of deionized water and heated at 170° C. for 21hours. The product was centrifuged, washed with absolute ethanol, driedovernight at 60° C., and then ground to a fine powder.

EXAMPLE 7 X-ray Characterization of Products

[0070] All of these materials produced in examples 4, 5 and 6 werecharacterized by x-ray diffraction to confirm their identity and purity.The diffraction patterns in FIG. 6 show how the crystallinity of sodiumnonatitanate improves with hydrothermal treatment. It should be notedthat all three patterns were normalized so that the highest peak has thesame value. In actual fact, the material treated for a week is a farmore efficient diffracter than either of the others.

EXAMPLE 8 Synthesis of Sodium Clinoptilolite

[0071] The sodium clinoptilolite used here was produced by processing anatural material. Purchased raw clinoptilolite was wet sieved (40-60mesh) and dried overnight at 100° C. A 100 g portion was then contactedwith 500 mL 0.1 M NaCl for 45 minutes with gentle agitation. Thesupernatant was decanted and discarded and the 0.1 M NaCl wash repeatedtwice. Na⁺ clinoptilolite was then washed two times with 500 mL Nanopurewater with a contact time of 5 minutes and subsequently dried overnightat 100° C. Samples used for screening experiments were ground to a finepowder.

EXAMPLE 9 Preliminary ⁹⁰Y/⁹⁰Sr Separations

[0072] An experiment was performed to assess the feasibility of usingthe inorganic ion exchange materials for separation of ⁹⁰Y from ⁹⁰Sr.Three materials were evaluated, namely KTS-Ph, NaTi and clinoptilolite.The KTS-Ph and NaTi had previously been formed into pellets 0.2-0.5 mmin diameter using polyacrylonitrile as a binder. The clinoptilolite wassupplied by BNFL Plc. of England and was already in granules suitablefor column use. Approximately 1 ml of each material was slurried into acolumn and 25 mL of a 0.05M NaOH/0.05M NaNO₃ solution containing 0.1 mCiof ⁹⁰Sr passed through the column over a period of approximately 5minutes. The liquid exiting the column was collected in 5 mL fractionsand counted using liquid scintillation counting (LSC). The samples werecounted again at a later date and the decrease in total counts recorded.The LSC spectra did not initially suggest the presence of ⁹⁰Sr (only⁹⁰Y) in any of the samples analyzed, indicating the absorption of nearly100% of the ⁹⁰Sr by the ion exchangers.

[0073] After allowing the samples to decay, a small amount of ⁹⁰Sr firstbecame visible in the spectra from the NaTi samples after 605 hours(9.45 half lives of ⁹⁰Y), by which time the ⁹⁰Y had decayed to less than0.2% of it's initial activity. Although it was not possible to quantifythe results with any certainty due to the contribution of ⁹⁰Y producedfrom the residual ⁹⁰Sr decay, an activity separation factor of ⁹⁰Sr/⁹⁰Yof about 1000 seems likely.

[0074] Liquid scintillation counting does not allow the simultaneousdetermination of ⁹⁰Sr and ⁹⁰Y since the spectra produced by the betaemissions from the two nuclides overlap significantly. Consequently, asolution containing the two isotopes produces a ‘two humped’ spectrumwith ⁹⁰Y at the higher energy end. By counting the samples containingthe partially purified ⁹⁰Y at different time intervals and knowing thehalf life of ⁹⁰Y, it is therefore possible to qualitatively note theappearance of ⁹⁰Sr as the contribution due to ⁹⁰Y decreases with time.Initially, the peak due to ⁹⁰Y swamps any minor peak corresponding to⁹⁰Sr, but as time progresses and the ⁹⁰Y decays, the ⁹⁰Sr componentbecomes more significant and can be discerned on the scintillationspectrum.

[0075] The pharmacosiderite performed even better than the NaTi withdefinite ⁹⁰Sr only being visible after 972 hours or over 15 ⁹⁰Yhalf-lives, by which time the ⁹⁰Y had decayed to less than 0.003% of itsinitial activity. Thus, a ⁹⁰Sr/⁹⁰Y separation factor of much greaterthan 1000 was achieved.

[0076] The clinoptilolite also showed no evidence of ⁹⁰Sr after 264hours (about 4 ⁹⁰Y half lives), but these experiments were terminatedprior to the appearance of ⁹⁰Sr.

[0077] Experiments were not performed to study the elutioncharacteristics of the ion exchangers, but it is clear that each of thematerials has a high affinity for ⁹⁰Sr and a low affinity for ⁹⁰Y indilute sodium nitrate solutions making them suitable candidates for usein a ⁹⁰Sr/⁹⁰Y generator system.

[0078] Although these preliminary experiments did not measure a specific⁹⁰Sr/⁹⁰Y separation factor, the results showed a very high ⁹⁰Sr/⁹⁰Yseparation suggesting that optimization of the loading and eluting stepsof the exchanger or the use of larger ion exchange beds (or multiplebeds) will allow the required separation factors of 10⁶ or greater to bereadily achieved.

[0079] The ion exchange capacity of the ion exchangers is variable, withclinoptilolite having the lowest capacity. Assuming a capacity of 2meq/g, a maximum of 1 mmol of Sr²⁺ can be loaded per gram of ionexchange material. The specific activity of ⁹⁰Sr is 50 Ci/g and,therefore, 1 mmol equates to 0.09 g. Thus, 9 Ci of ⁹⁰Sr can be loadedonto 1 g of ion exchange material. This means that ion exchangerconsumption will be minimal and thus will constitute a very minorproportion of the generator costs. Using an estimated cost of the $1,000per kilogram for the ion exchange material, the cost of the ionexchanger will be only $1 per gram, and thus will constitute anegligible part of the total generator cost.

EXAMPLE 10 Evaluation of Ion Exchange Materials

[0080] A total of eight potentially useful ion exchange materials andone potential binder were identified. These are listed in Table 3, alongwith the abbreviation used in subsequent tables and figures. The firststep is to evaluate the affinity of the selected ion exchange materialsfor strontium as a function of salt concentration. TABLE 3 Inorganic IonExchange Materials Evaluated in Batch Tests Material AbbreviationChabazite (commercial product) AW-500 Potassium pharmacosiderite(synthesized) TA-A-2 Sodium titanosilicate (synthesized) TA-A-13 Sodiumnonatitanate (synthesized and hydrothermally TA-A-17 treated for sevendays) Sodium nonatitanate (synthesized with no hydrothermal TA-A-18treatment) Sodium nonatitanate (synthesized and hydrothermally TA-A-19treated for 21 hours) Sodium nonatitanate (commercial product) HoneywellTitanium-based binder material (synthesized through Hydro TiO₂ thehydrolysis of Ti(i-OPr)₄) Sodium clinoptilolite (commercial productexchanged Clino Na⁺ into sodium form)

[0081] Samples were evaluated using a simple batch technique to allowthe rapid screening of a large number of materials with multiplecomplexants. Blanks were run for each matrix to check for any loss ofstrontium/yttrium during filtration or absorption of strontium/yttriumonto the scintillation vials. In all solutions evaluated, strontiumabsorption in the experimental blanks was negligible.

[0082] In each case 0.05 g of ion exchange materials was contacted with10 ml of a solution, spiked with either ⁸⁹Sr or ⁸⁸Y, in a cappedscintillation vial. (Solutions spiked with ⁸⁸Y were filtered immediatelybefore use to remove precipitated yttrium. Experience with ⁸⁹Sr hasshown that no precipitation occurs and they were not filtered beforeuse.) The mixtures were shaken for 6 hours, filtered through a 0.2 μmsyringe filter and the residual activity determined using liquidscintillation counting (LSC). Distribution coefficients (K_(d) values)were then determined according to the following equation:

K_(d)=((A_(i)−A_(f))/A_(f))×(v/m)  (2)

[0083] where: A_(i) is the initial activity in solution (counts perminute/mL)

[0084] A_(f) is final activity in solution (counts per minute/mL)

[0085] v is the volume of the solution (mL), and,

[0086] m is the mass of exchanger (g)

[0087] The final pH of the solution was also noted. Six hours was chosento allow equilibrium to be reached for each of the ion exchangematerials. This period is more than adequate. Previous research hasshown that the kinetics for reactions of this type are very rapid andthat they generally proceed to >>95% completion in less than fiveminutes. All experiments were performed in duplicate, and, ifsignificant variations between duplicate samples occurred, theexperiments were repeated until good agreements on the K_(d) values wereobtained.

[0088] Table 4 shows how the strontium distribution coefficients varyfor eight ion exchange materials as the salt concentration is varied bythree orders of magnitude. These results are presented here because thisdata was used in the design of the rest of the experiments. TheNa-clinoptilolite shows the greatest variation with concentration, 3½orders of magnitude. The strontium selectivity of both of the zeolitesdecreased significantly in higher ionic strength solutions, thuslimiting their use to less saline solutions. (This is actually anadvantage, because a requirement for high electrolyte content, e.g.,high salinity, could add complexity to later steps in the preparation ofthe final pharmaceutical.) Most materials showed one order of magnitudeof variation or less. TABLE 4 Effect of NaCl Concentration on theDistribution Coefficient for Strontium Ion Exchange Material 1 M NaCl0.1 M NaCl 0.01 M NaCl 0.001 M NaCl Clino Na⁺ 8 124 3,260 36,900 AW-5001,860 88,300 1,270,000 1,210,000 TA-A-13 556,000 273,000 119,000 42,900TA-A-2 18,300 251,000 594,000 281,000 Honeywell 80,600 1,030,000 258,000166,000 TA-A-18 1,530,000 2,570,000 739,000 372,000 TA-A-19 1,030,0001,240,000 272,000 172,000 TA-A-17 167,000 834,000 264,000 90,400

EXAMPLE 11 Effectiveness of Complexing Agents

[0089] To evaluate the effectiveness of the complexant 0.45 μCi of ⁸⁸Y(a β⁺ [positron] emitter with a 107 day half-life) was added to a seriesof solutions each 0.01 M in NaCl concentration and 0.001 M in one of thenine complexants. (A blank was also run.) The test was repeated sixtimes with the pH adjusted to a different value each time. In each casethe solution was stirred for an hour and filtered. The amount of yttriumremaining in solution was determined by LSC of the filtered solution.The effectiveness of the complexants was evaluated by comparing theamount of yttrium remaining in solution with the complexant with theamount remaining in solution without any complexant. Seven of thecomplexants were found to improve the solubility of yttrium and five ofthese were selected for further study. Although both EDTA and HEDTA werefound to be quite effective in this test, they were eliminated fromfuture testing because they also suppress the retention of strontium onthe ion exchange material. The complete results appear in Table 5. TABLE5 Fraction of ⁸⁸Y Remaining in Solution with each Complexant pH 5 pH 7pH 9 pH 10 pH 12 pH 13 Blank 78% 64% 61% 46% 61% 34% D-Gluconic Acid 84%85% 81% 74% 89% 87% Oxalic Acid 110% 111% 103% 93% 42% 16% Glycolic Acid66% 57% 56% 55% 79% 20% Iminodiacetic Acid 94% 93% 71% 49% 63% 72%Nitriloacetic Acid 97% 98% 85% 99% 107% 60% Citric Acid 91% 98% 99% 96%103% 34% Acetic Acid 49% 25% 14% 19% 24% 28% HEDTA 92% 104% 92% 86% 100%89% EDTA 91% 103% 84% 100% 100% 95%

EXAMPLE 12 Distribution Coefficients in the Presence of ComplexingAgents

[0090] The results shown in Table 4 and Table 5 supply the basis for thetesting carried out in this and subsequent examples. The formulae andstructures of the complexants selected for the next series ofexperiments are shown in FIG. 6.

[0091] The strontium and yttrium selectivity of the chosen ion exchangematerials were evaluated in six different solutions (0.01M NaCl, 0.01MNaCl/0.001M gluconic acid, 0.01M NaCl/0.001M oxalic acid, 0.01MNaCl/0.001M iminodiacetic acid, 0.01M NaCl/0.001M nitrilotriacetic acid,and 0.01M NaCl/0.001M citric acid) using radiotracer techniques. EDTAand HEDTA were not evaluated because previous studies had indicated thatthe ion exchange materials had a reduced affinity for strontium in EDTAand HEDTA solutions. The other complexants did not significantlydecrease the strontium affinity.

[0092] The distribution coefficients for both yttrium and strontium wereevaluated using the same batch technique with radiotracers as wasdescribed in example 10, above. The six hour equilibration time allowedin these experiments is clearly more than adequate. Previous researchhas shown that the kinetics for reactions of this type are very rapidand that they generally proceed to >>95% completion in less than fiveminutes.

[0093] Table 6 shows the results of the batch tests for strontium witheach of the five selected complexants and with no complexant. In allcases the strontium was strongly absorbed onto the ion exchangematerial. The poorest performer was the material intended to serve asthe binder.

[0094] Table 7shows the results of the batch tests for yttrium with eachof the five selected complexants and with no complexant. In general,yttrium was not retained as effectively as strontium. This is thedesired result.

[0095] Ideally we would like to have an ion exchange material with anexceptionally high affinity for strontium and no affinity for yttrium.Fortunately for ion exchange purposes strontium is coordinated by watermuch more loosely than yttrium. This means that in solution the morehighly charged yttrium is effectively a much larger cation than thestrontium, and has a greater tendency to be excluded from sites insidethe cage or layer structure of the ion exchange materials. TABLE 6Distribution Coefficients (K_(d)) for Strontium Complexant Imino-Nitrilo- Ion Gluconic Oxalic diacetic triacetic Citric Exchangers NoneAcid Acid Acid Acid Acid AW-500 20,750 14,072 14,544 15,289 6,447 13,236TA-A-2 19,789 17,617 14,425 15,591 2,734 14,669 TA-A-13 16,746 11,43113,809 14,839 10,859 14,899 TA-A-17 19,728 17,214 17,464 16,326 11,71016,520 TA-A-18 20,761 18,430 14,859 16,146 16,995 16,451 TA-A-19 20,64317,973 17,651 16,572 16,573 13,022 Honeywell 21,091 18,440 15,195 17,56210,014 18,178 Hydro TiO₂ 21.40 825.1 782.4 66.10 169.0 1,213 Clino Na⁺301.6 533.7 910.0 283.8 314.6 180.4

[0096] TABLE 7 Distribution Coefficients (K_(d)) for Yttrium ComplexantImino- Nitril- Ion Gluconic Oxalic diacetic triacetic Citric ExchangersNone Acid Acid Acid Acid Acid AW-500 6,772 87.20 36,252 6,320 1.00 230.6TA-A-2 11,209 1,471 31,141 9,554 2.25 29,897 TA-A-13 6,763 233.0 20,4298,041 60.65 20,592 TA-A-17 25,616 1,691 67,241 15,678 7,408 73,261TA-A-18 23,330 2,443 115,936 20,650 13,468 97,918 TA-A-19 31,606 4,36793,683 22,510 13,528 40,210 Honeywell 21,279 8,223 68,311 20,673 36140,000 Hydro TiO₂ 254,917 36,247 247,610 61,410 638 36,702 Clino Na⁺10,755 111.0 42,944 204.5 0.35 38.80

[0097] The key to selecting a combination of ion exchange material andcomplexant is maximizing the ratio of the strontium K_(d) to the yttriumK_(d). The complete set of ratios appears in Table. It is clear fromthis data that nitrilotriacetic acid (NTA) produces the highest ratio inevery case where Sr is substantially more tightly bound than Y. TABLE 8Ratio of Distribution Coefficients (K_(d)) for Strontium and YttriumComplexant Imino- Nitrilo- Ion Gluconic Oxalic diacetic tracetic CitricExchangers None Acid Acid Acid Acid Acid AW-500 3.06 161 0.40 2.42 6,44757.4 TA-A-2 1.77 12.0 0.46 1.63 1,215 0.49 TA-A-13 2.48 49.0 0.68 1.85179 0.72 TA-A-17 0.77 10.2 0.26 1.04 1.58 0.23 TA-A-18 0.89 7.54 0.130.78 1.26 0.17 TA-A-19 0.65 4.12 0.19 0.74 1.23 0.32 Honeywell 0.99 2.240.22 0.85 27.8 0.45 Hydro TiO₂ 0.00 0.02 0.00 0.00 0.26 0.03 Clino Na⁺0.03 4.81 0.02 1.39 899 4.65

[0098] The data from Table 8 is illustrated graphically in FIG. 8. Thedata has been plotted on a log scale to render the relative size of thebars at Sr:Y ratios less than 100 (10²) more apparent. (If plotted on alinear scale, only three bars are visible.) Bars extending upward fromthe central plane (at a ratio of 10⁰, or 1) indicate combinations thatfavor the retention of strontium over yttrium. Bars extending downwardfrom the plane indicate combinations favoring the retention of yttriumover strontium.

[0099] It is clear from these results that NTA, citric acid, andgluconic acid are the most effective complexants, improving the ionexchanger's preference for Sr over Y in most cases. As shown in both thetable and the figure, most of the ion exchange materials had littlepreference for either ion in the absence of a complexant. (Oxalic acidcauses the ion exchangers to prefer Y to Sr, possibly due to aprecipitation reaction.) Based on these results four ion exchangers wereselected for column testing, chabazite (AW-500), sodium titanosilicate(TA-A-13), clinoptilolite, and potassium pharmacosiderite (TA-A-2).

EXAMPLE 13 Preparation of Generator Columns

[0100] Materials produced as powders were pelletized using an inorganicbinder and all materials sized with a 40-60 mesh portion selected fortesting.

[0101] For each of the ion exchangers to be tested sufficient materialto fill a 1 mL-bed volume of 40-60 mesh sized particles was slurried indeionized water and poured into ion exchange columns (internal diameter0.7 cm). The column beds were then washed by passing 50 mL of deionizedwater through each to remove any remaining fines. To prevent the escapeof any pelletized ion exchange material which might be released duringthe course of experiments due to mechanical degradation of thepelletized material 0.2 μm syringe filters were then attached to theeffluent end of each column.

[0102] Two columns were prepared for three of the ion exchange thematerials (sodium titanosilicate, chabazite, and clinoptilolite) withthree columns prepared with the potassium pharmacosiderite.

[0103] Individual columns were loaded with ⁹⁰Sr by passing a 20 mL 0.01M NaOH solution spiked with 0.1 mCi ⁹⁰Sr/0.05 mCi ⁸⁵Sr through each at aflow rate of approximately 20 mL/hr. The flow rate through each columnwas maintained by a peristaltic pump that pulled solutions thoughcolumns and into collection vessels through {fraction (1/16)}″ i.d.Tygon tubing. Strontium uptake was found to be virtually quantitative inall cases. Each column was then washed by passing 20 mL 0.01 M NaClthrough the column then bringing the liquid level inside the column downto the top of the ion exchange bed. Columns were then stored until theirrespective weekly elution.

[0104]FIG. 9 shows one of the ion exchange columns 10 having an effluentfilter 12 and filled with pellets 14 of an ion exchange material, suchas sodium titanosilicate.

EXAMPLE 14 Column Tests

[0105] Seven days after the initial loading, a weekly elution routinewas established for each column and maintained until data collection wascomplete. For each elution, a 10 mL aliquot of chosen complexant/eluant(pH was varied throughout course of project) was passed through eachcolumn at a flow rate of 80 mL per hour. Portions of the resulting 10 mLeluate were analyzed by both liquid scintillation counting (1 mL) andgamma counting (9 mL) and the final pH of the solution recorded.

[0106] Following elution, each column was washed by passing 20 mL of0.01 M NaCl (pH 6.1±0.05) through each at a flow rate of 80 mL per hour.The resultant 20 mL wash eluate was analyzed by liquid scintillationcounting (1 mL) and gamma counting (19 mL) and the pH recorded. Columnswere then stored until their next cycle of weekly elutions/washing wereperformed.

[0107] Each column was milked on a weekly basis and the ingrown ⁹⁰Yeluted using a series of eluants.

EXAMPLE 15 Column Tests with Chabazite

[0108] The procedures described in example 14 were carried out usingchabazite (AW-500). FIG. 10 shows the ⁹⁰Y yields obtained with a seriesof three eluants, 0.001 M NTA in 0.01 M NaCl (for the first threeweeks), 0.01 M NaCl alone (week four), and 0.001 M (weeks five andeight) and 0.003 M citric acid in 0.01 M NaCl (weeks six and seven).

[0109] It's clear that both NTA and citric acid are effectivecomplexants for the selective elution of ⁹⁰Y from a ⁹⁰Sr cow. Theresults shown here were obtained by scintillation counting to measurethe β-decay activity of the ⁹⁰Y isotope. ⁹⁰Sr is also a β emitter makingit impossible to determine if trace amounts of ⁹⁰Sr are being lost fromthe column. When ⁹⁰Sr gets into the human body it rapidly deposits inbones and due to its long half-life, it is a major health risk that mustbe avoided, and can be avoided by insuring that a ⁹⁰Y generator issufficiently selective. By adding ⁸⁵Sr, a γ-emitter, to the ⁹⁰Sr loadedon the column, even a small loss of strontium during milkings can bemeasured using a gamma counter. Using this technique there was noevidence of any strontium loss from the AW-500.

EXAMPLE 16 Column Tests with Sodium Titanosilicate

[0110] The procedures described in example 14 were carried out usingchabazite (AW-500). FIG. 11 shows the milking results using sodiumtitanosilicate carried out with the eluents initially in the same orderas described in example 15. This ion exchanger performed well with NTA,but not with citrate. Because of its consistent poor performance withcitrate as the complexant it was also tested with gluconic acid as thecomplexant. This complexant failed to produce an improvement. Likechabazite, there was no evidence of Sr leaching.

EXAMPLE 17 Column Tests with Clinoptilolite

[0111] The procedures described in example 14 were carried out usingclinoptilolite. FIG. 12 shows the ⁹⁰Y milking results for the columnsloaded with clinoptilolite carried out with the eluents in the sameorder as described in example 15. The results look quite good, but thereis a problem. FIG. 13 shows the results for leaching Sr from the cow.Although the levels of ⁸⁵Sr detected are low, the release isunacceptable if clinoptilolite is to be used in a ⁹⁰Y generator. Thisloss of strontium concurs with the data shown in Table, whichdemonstrates the low affinity of clinoptilolite for strontium incomparison with the other ion exchange materials evaluated.

EXAMPLE 18 Column Tests with Potassium Pharmacosiderite

[0112] The procedures described in example 14 were carried out usingpotassium pharmacosiderite. FIG. 14 shows the ⁹⁰Y elution results forpotassium pharmacosiderite carried out with the eluents initially in thesame order as described in example 15. Like sodium titanosilicate, thismaterial is an effective absorbent for ⁹⁰Sr when NTA is used as thecomplexant, but less effective with citrate. Because of its consistentpoor performance with citrate as the complexant, it was also tested withgluconic acid as the complexant. This complexant failed to produce animprovement. Unlike sodium titanosilicate, it also leaches a smallamount of strontium with NTA, as shown in FIG. 15. Although the amountof strontium lost is an order of magnitude less than observed forclinoptilolite, it is still too great to allow the material to be usedin a ⁹⁰Y generator.

EXAMPLE 19 Stability of the Inorganic Ion Exchange Material

[0113] Examples 15 through 18 above are directed to demonstrating howwell an inorganic ion exchange column performs for the primary task in a⁹⁰Y generator. It is also important to know how a column willmechanically degrade with use. To determine this two columns werefabricated, one with chabazite (AW-500) containing a quadruple loading(4 mL bed volume) and the other with sodium titanosilicate (standard 1mL bed volume). They were each connected to a peristaltic pump andsubjected to a flowing stream of 0.003 M citric acid in 0.01 M NaClmaking a single pass through the bed at a flow rate of 80 mL/h for over24 hr. Samples of the solution were collected and analyzed by atomicabsorption spectroscopy (AA) for Si, Al, and Ti.

[0114] The results from the stability tests carried out on the unloadedcolumns appear in Table 9. The values given are the concentration of themetal ions observed in the complexant solution after passing through thecolumn. The higher than expected levels of Al and Si are attributed tothe clay binder used in the fabrication of the pellets. This is afeature that can be changed by starting with unpelletized chabazite andusing a more stable binder. At the concentrations being evaluated here,AA is of marginal utility in measuring the concentrations of these ionsand the results are only approximate. It is safe to say that there islittle, if any, extraction of ions from the ion exchange materialoccurring. TABLE 9 Ions in Solution Al Si Ti (ppm) (ppm) (ppm) Blankn.d. n.d. n.d. AW-500 27 35 n.d. TA-A-13 n.d. n.d. n.d.

[0115] While the foregoing is directed to the preferred embodiment ofthe present invention, other and further embodiments of the inventionmay be devised without departing from the basic scope thereof, and thescope thereof is determined by the claims that follow. It will beunderstood from the foregoing description that various modifications andchanges may be made in the preferred embodiment of the present inventionwithout departing from its true spirit. It is intended that thisdescription is for purposes of illustration only and should not beconstrued in a limiting sense. The scope of this invention should belimited only by the language of the following claims.

[0116] In the present specification “comprises” means “includes” and“comprising” means including” and these terms do not exclude theinvolvement other components or steps.

[0117] The features disclosed in the foregoing description, or thefollowing claims, or the accompanying drawings, expressed in theirspecific forms or in terms of a means for performing the disclosedfunction, or a method or process for attaining the disclosed result, asappropriate, may, separately, or in any combination of such features, beutilised for realising the invention in diverse forms thereof.

What is claimed is:
 1. A process, comprising: adsorbing strontium-90onto an inorganic ion exchange material from an aqueous solutioncomprising a source of strontium-90; and eluting yttrium-90 from theinorganic ion exchange material with a solution having a pH greater thanabout 5 and including a chelating agent.
 2. The process of claim 1,wherein the solution is aqueous.
 3. The process of claim 1, wherein thechelating agent is selected from gluconic acid, oxalic acid,iminodiacetic acid, nitrilotriacetic acid, citric acid, and combinationsthereof.
 4. The process of claim 1, where the solution is neutral. 5.The process of claim 1 where the solution is alkaline.
 6. The process ofclaim 1, wherein the inorganic ion exchange material is selected fromclinoptilolite, chabazite, potassium titanosilicate pharmacosiderite,sodium titanosilicate, sodium nonatitanate, and combinations thereof. 7.The process of claim 6, wherein the aqueous solution includes achelating agent selected from gluconic acid, oxalic acid, iminodiaceticacid, nitrilotriacetic acid, citric acid, and combinations thereof. 8.The process of claim 1, wherein the inorganic ion exchange material issodium nonatitanate prepared by reacting titanium isopropoxide andaqueous sodium hydroxide at a temperature between 100° C. and 250° C.for a period between 12 hours and 2 weeks.
 9. The process of claim 1,wherein the inorganic ion exchange material is sodium titanosilicateprepared by hydrothermally heating a titanium silicate gel in NaOH. 10.The process of claim 9, wherein the titanium silicate gel ishydrothermally heated in 6M NaOH at 170° C. for 2 days.
 11. The processof claim 1, wherein the inorganic ion exchange material is atitanosilicate having the general formula: M₃H(AO)₄(BO₄)₃ .xH₂O where: Mis a cation selected from H, K, Na, Rb, Cs and mixtures thereof; A isselected from Ti and Ge; and B is selected from Si and Ge; and x is avalue between 4 and
 6. 12. The process of claim 1, further comprisingforming the inorganic ion exchange material into pellets.
 13. Theprocess of claim 12, wherein the pellets are formed with an averagediameter between 0.1 and 1.0 mm.
 14. The process of claim 12, whereinthe pellets are formed with an average diameter between 0.2 and 0.5 mm.15. The process of claim 12, wherein the pellets comprise a polymericbinder.
 16. The process of claim 15, wherein the polymeric bindercomprises polyacrylonitrile as a binder.
 17. The process of claim 12,wherein the pellets comprise an inorganic binder.
 18. The process ofclaim 17, wherein the inorganic binder is amorphous.
 19. The process ofclaim 17, wherein the pellets comprise an inorganic binder selected fromamorphous titanium dioxide, amorphous silica, amorphous zirconium oxide,and combinations thereof.
 20. A process, comprising: (a) preparing afirst solution including strontium-90; (b) adsorbing strontium-90 fromthe first solution onto an inorganic ion exchange material; and (c)allowing yttrium-90 to grow into the inorganic ion exchange material;and (d) eluting yttrium-90 from the inorganic ion exchange material witha second solution including a chelating agent.
 21. The process of claim20, further comprising: repeating steps (c) and (d).
 23. The process ofclaim 20, wherein the inorganic ion exchange material is selected fromclinoptilolite, chabazite, potassium titanosilicate pharmacosiderite,sodium titanosilicate, sodium nonatitanate, and combinations thereof.24. The process of claim 20, wherein the first solution has a pH greaterthan about
 5. 25. The process of claim 20, wherein the second solutionhas a pH greater than about
 5. 26. The process of claim 20, where thesecond solution is neutral.
 27. The process of claim 20, where thesecond solution is alkaline.
 28. The process of claim 20, wherein thesecond solution includes a chelating agent.
 29. The process of claim 28,wherein the chelating agent is selected from gluconic acid, oxalic acid,iminodiacetic acid, nitrilotriacetic acid, citric acid, and combinationsthereof.
 30. The process of claim 20, further comprising: (e) washingthe inorganic ion exchange material to remove poorly bound strontium-90prior to eluting.